Although the importance of the thymus gland to immunologic function has been recognized for several years, it is only recently that an interrelatonship between the thymus and the reproductive system has become apparent. The congenitally athymic nude (nu/nu) mouse, which is known to have severe abnormalities in reproductive function, offers an ideal animal model in which to study this interaction. We have recently demonstrated that both gonadotropin and gonadal steroid secretion are reduced in athymic mice, both male and female, in comparison to their endocrinologically normal heterozygous (nu/plus) littermates. We propose to extend these preliminary findings by examining the function of the hypothalamic-hypophyseal unit and of the ovaries and testes in vivo and in vitro. Specifically, the hypothalamic content of luteinzing hormone-releasing factor (LRF) and catecholamines and the response of the pituitary to exongenous LRF will be determined in athymic mice and their normal littermates. The ability of pituitary and gonadal cells to respond to LRF and to exongenous gonadotropins, respectively, in vitro will be assessed as well. Investigations to determine if the nature of this thymic influence is humoral will also be conducted. The results of these experiments should provide basic information about the interaction between immune and endocrine systems central to developmental biology and normal and abnormal sexual differentiation. Furthermore, an understanding of the mechanism(s) underlying the increased follicular atresia present in female athymic mice should provide rationale for the treatment of premature ovarian failure in the human.